In recent years, rapid progress of stem cell studies has increased momentum toward regenerative medicine, and the knowledge and understanding thereof have been widespread not only in researchers but also in the public. Regenerative medicine using stem cells is medicine intended for reestablishing the function of cells and tissues damaged by various diseases by utilizing the self-renewal potential and pluripotency of stem cells or factors secreted by stem cells. Bone-marrow transplantation in patients having intractable hematological diseases such as leukemia and aplastic anemia results in the engraftment of hematopoietic stem cells in the body of these patients, which permits the maintenance of hematopoietic capacity over almost their entire life. Recently, many researchers have aimed at clinical application using stem cells other than hematopoietic stem cells, have identified stem cells in the central nerves, peripheral nerves, bone marrow, small intestine, and the like, and stem cell transplantation treatment has been started for traumatic disease and tissue degeneration disease (Non-patent Documents 1 to 3).
For efficient transplantation of mammalian stem cells into a target damaged site (an affected site), it is considered to be important to optimize a method (route) for transplantation of stem cells. To date, mainly 4 types of methods, i.e., a stereotactic (direct) transplantation method, an intrathecal (intracerebrospinal) transplantation method, an intravenous transplantation method, and an intraarterial transplantation method, are known as transplantation methods for stem cells. Among these, the stereotactic transplantation method is a method which involves transferring stem cells directly into an affected site. Use of the stereotactic transplantation method can increase the number of engrafting donor's stem cells because of direct administration into an affected site, thus decreasing the number of administered stem cells, although the method is slightly invasive. The intrathecal transplantation method is a method which involves intrathecally transferring stem cells by ventriculopuncture. The intrathecal transplantation method is a method which has been studied mainly for the treatment of brain diseases such as cerebral infarction, cerebral contusion, and spinal cord damage; however, it still leaves many problems in the clinical application thereof, such as the potential risk of the ventriculopuncture causing new cerebral damage.
The intravenous transplantation method and the intraarterial transplantation method are methods for transferring cells such as stem cells intravenously and intraarterially, respectively (methods for administration through the blood vessels). Use of the method for administration through a blood vessel is less invasive and can systemically circulate cells such as stem cells and factors secreted by cells such as stem cells, although it decreases the number of engrafting donor's liver cells compared to the use of the stereotactic transplantation method. At present, a method involving intravenously transplanting mesenchymal stem cells (MSC) for cerebral infarction disease, a method involving intravenously transplanting mononuclear cells for cerebral infarction disease, a method involving intravenously transplanting pancreatic islet cells into type I diabetes patients, and the like are known as clinically performed methods for administration through a blood vessel.
As a risk when cells such as stem cells are transplanted using the method for administration through a blood vessel, it has been pointed out that intraarterially or intravenously administered cells get clogged in capillary blood vessels of the pulmonary artery (pulmonary embolism) in passing through the lung, resulting in reduced pulmonary and cardiac function (pulmonary embolic disease) and, in some cases, posing a risk of leading to death. To prevent pulmonary embolism formation and pulmonary embolic disease, stem cells are transplanted in clinical sites while monitoring the partial pressure of oxygen in the peripheral blood during the administration of stem cells by a pulse oximeter.
Meanwhile, trehalose is a type of disaccharide formed by the 1,1-glycosidic linkage of two glucose molecules. Trehalose is used in various foods and cosmetics because it presents a sweet taste and has a high water retaining capacity. Trehalose is also used as an active ingredient of an organ-protecting solution in transplanting the organ because it has the properties of stabilizing cell membrane and suppressing cell damage. Excellent organ preservation solutions containing trehalose have been developed, such as ET-Kyoto solution and New ET-Kyoto solution (Patent Documents 1 and 2 and Non-patent Document 4). However, it has been unclear whether the risk of pulmonary embolism formation by cells is reduced or not or pulmonary embolic disease is prevented or not when cells such as stem cells are suspended in a trehalose-containing solution and the cell suspension is administered through a blood vessel.